The principal aim of this proposal is to study the transcriptional control of cell growth during myocardial hypertrophy. The myocardium is composed of two cell types: muscle and non-muscle cells. Cardiac muscle cells respond to a pressure overload by an increase in size whereas the non-muscle cells increase in number. What regulates these changes is not known. Increased protein synthesis during cardiac hypertrophy is accompanied by an increase in RNA synthesis. This suggest that cell growth during myocardial hypertrophy may be regulated at the transcriptional level by changes in either RNA polymerase or DNA template activity. In this proposal we will measure RNA polymerase activity and examine the acidic non-histone nuclear proteins which may regulate DNA template activity in separate cardiac muscle and non-muscle cells during the development and regression of pressure-overload induced myocardial hypertrophy. Cardiac muscle and non-muscle cells will be separated by enzymatic dissociation followed by differential sedimentation. This method separates the two cell types with minimal cross-contamination. The project is divided into four main phases. In phase I the various RNA polymerases from muscle and non-muscle cells will be solubilized, fractionated by chromatography and characterized. Changes in solubilized RNA polymerase activity with exogenous DNA template will be studied. In the second phase the template activities of chromatin from normal and hypertrophied myocardium will be compared to determine what changes in template activity occur during myocardial hypertrophy. In the third phase of this proposal we will study acidic non-histone nucleoproteins from muscle and non-muscle cells during hypertrophy. We are specifically interested in examining changes in their distribution according to molecular weight, their ability to stimulate chromatin directed RNA polymerase activity, their binding to DNA and the importance of phosphorylation. Finally, we will examine the role poly (ADP-ribose) may have in the regulation of transcription.